Parathyroid hormone-related protein (PTHrP) is now understood to be the peptide hormone responsible for the majority of instances of humoral hypercalcemia of malignancy (HHM). The posttranslational processing of PTHrP is rapidly being elucidated. One of the normal secretory forms of the peptide has been shown to be PTHrP (1-36), Despite these recent advances, certain aspects of the pathophysiological picture in HHM remain unclear. Specifically, it is unclear whether and to what extent PTHrP plays a role in renal calcium reabsorption. Second, it is unclear why and how the regulation of plasma 1,25(OH)2 vitamin D differs between patients with HHM and those with primary hyperparathyroidism. Third, it is unclear how and why osteoclast-osteoblast activities, which are coupled in primary hyperparathyroidism, are uncoupled in HHM. Finally, both PTH (1-34) and amino-terminal PTHrP have been shown to be anabolic in terms of their ability to augment skeletal mass in animal models. The first human studies employing hPTHrP(1-36) have recently been completed in the applicant's laboratory. These pilot studies have shown that hPTHrP (1-36) is as potent as hPTH(1-34) as a calcium-mobilizing hormone in human beings. The studies will expand these pilot studies.